Method and apparatus for minimizing post-infarct ventricular remodeling

ABSTRACT

A cardiac rhythm management device is configured to deliver pre-excitation pacing to one or more sites in proximity to an infarcted region of the ventricular myocardium. The pre-excitation pacing in conjunction with counterpulsation therapy serves to either prevent or minimize post-infarct remodeling.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/862,011, filed Jun. 4, 2004, now issued as U.S. Pat. No. 7,450,988,which is hereby incorporated by reference in its entirety.

This application is related to U.S. patent application Ser. No.10/005,184, filed on Dec. 5, 2001, now issued as U.S. Pat. No.6,973,349, the disclosure of which is incorporated by reference in itsentirety.

FIELD OF THE INVENTION

This invention pertains to cardiac rhythm management devices such aspacemakers and other implantable devices.

BACKGROUND

A myocardial infarction is the irreversible damage done to a segment ofheart muscle by ischemia, where the myocardium is deprived of adequateoxygen and metabolite removal due to an interruption in blood supply. Itis usually due to a sudden thrombotic occlusion of a coronary artery,commonly called a heart attack. If the coronary artery becomescompletely occluded and there is poor collateral blood flow to theaffected area, a transmural or full-wall thickness infarct can result inwhich much of the contractile function of the area is lost. Over aperiod of one to two months, the necrotic tissue heals, leaving a scar.The most extreme example of this is a ventricular aneurysm where all ofthe muscle fibers in the area are destroyed and replaced by fibrous scartissue.

Even if the ventricular dysfunction as a result of the infarct is notimmediately life-threatening, a common sequela of a transmuralmyocardial infarction in the left ventricle is heart failure broughtabout by ventricular remodeling. Heart failure refers to a conditionwhere cardiac output falls below a level adequate to meet the metabolicneeds of the body which, if uncompensated, leads to rapid death. Onephysiological compensatory mechanism that acts to increase cardiacoutput is the increased diastolic filling pressure of the ventricles asan increased volume of blood is left in the lungs and venous system.This increases the preload, which is the degree to which the ventriclesare stretched by the volume of blood in the ventricles at the end ofdiastole. An increase in preload causes an increase in stroke volumeduring systole, a phenomena known as the Frank-Starling principle.

Left ventricular remodeling is a physiological process in response tothe hemodynamic effects of the infarct that causes changes in the shapeand size of the left ventricle. Remodeling is initiated in response to aredistribution of cardiac stress and strain caused by the impairment ofcontractile function in the infarcted area as well as in nearby and/orinterspersed viable myocardial tissue with lessened contractility due tothe infarct. The remodeling process following a transmural infarctionstarts with an acute phase which lasts only for a few hours. Theinfarcted area at this stage includes tissue undergoing ischemicnecrosis and is surrounded by normal myocardium. Until scar tissueforms, the infarcted area is particularly vulnerable to the distendingforces within the ventricle and undergoes expansion over a period ofhours to days as shown in a second phase of remodeling. Over the nextfew days and months after scar tissue has formed, global remodeling andchamber enlargement occur in a third phase due to complex alterations inthe architecture of the left ventricle involving both infarcted andnon-infarcted areas. Remodeling is thought to be the result of a complexinterplay of hemodynamic, neural, and hormonal factors.

The ventricular dilation resulting from the increased preload causesincreased ventricular wall stress at a given systolic pressure inaccordance with Laplace's law. Along with the increased pressure-volumework done by the ventricle, this acts as a stimulus for compensatoryhypertrophy of the ventricular myocardium. Hypertrophy can increasesystolic pressures but, if the hypertrophy is not sufficient to meet theincreased wall stress, further and progressive dilation results. Thisnon-compensatory dilation causes wall thinning and further impairment inleft ventricular function. It also has been shown that the sustainedstresses causing hypertrophy may induce apoptosis (i.e., programmed celldeath) of cardiac muscle cells. Thus, although ventricular dilation andhypertrophy may at first be compensatory and increase cardiac output,the process ultimately results in further deterioration and dysfunction.It has been found that the extent of left ventricular remodeling in thelate period after an infarction, as represented by measurements ofend-systolic and end-diastolic left ventricular volumes, is an even morepowerful predictor of subsequent mortality than the extent of coronaryartery disease. Preventing or minimizing such post-infarct remodeling isthe primary concern of the present invention.

SUMMARY

The present invention relates to a method and apparatus for minimizingthe ventricular remodeling that normally occurs after a myocardialinfarction. The part of the myocardium that is most vulnerable to thepost-infarct remodeling process is the infarct region, which is an areathat includes sites in and around the infarct where the myocardialfibers are still intact but contractile function is impaired. Theinfarct region is thus the area most likely to undergo the progressivenon-compensatory dilation described above with wall thinning and furtherimpairment of function. By pacing myocardial sites in proximity to theinfarct with appropriately timed pacing pulses, the infarct region ispre-excited in a manner that lessens the mechanical stress to which itis subjected, thus reducing the stimulus for remodeling. Furtherdecreases in myocardial wall stress may be obtained by combining thepacing therapy with counterpulsation therapy, applied either externallyor with intra-aortic balloon pumping.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an exemplary cardiac rhythm managementdevice for delivering pre-excitation pacing.

FIG. 2 illustrates a pacemaker and an exemplary pacing configuration.

FIG. 3 illustrates a multi-site electrode arrangement.

FIGS. 4A through 4C illustrate examples of patch electrodes formulti-site pacing.

FIG. 5 illustrates an exemplary system for delivering counterpulsationtherapy and pre-excitation pacing.

DETAILED DESCRIPTION

When a transmural myocardial infarction in the left ventricle occurs,the affected area suffers a loss of contractile fibers that depends uponthe degree of collateral circulation to the area. For example, theinfarction may either leave a non-contractile scar or leave some viablemyocardium interspersed with scar tissue, with the myocardial fibersthat surround the infarcted area suffering a variable amount ofdestruction. In any case, regions in and around the infarct sufferimpaired contractility, and it is this impairment that is responsiblefor the ventricular dysfunction that initiates the remodeling process asdescribed above. Whether the infarction results in a non-contractilescar or a fibrous region with diminished contractility, the viablemyocardium in proximity to the infarct are the regions of the ventriclethat are least able to respond to the increased stresses brought aboutby ventricular dysfunction in a physiologically appropriate manner.These regions are thus the parts of the ventricle that are mostvulnerable to the post-infarct remodeling process. If a way could befound to subject the regions in proximity the infarct to lessenedmechanical stress without unduly compromising ventricular systolicfunction, the undesirable remodeling of the region could be prevented orminimized.

The degree to which a heart muscle fiber is stretched before itcontracts is termed the preload, while the degree of tension or stresson a heart muscle fiber as it contracts is termed the afterload. Themaximum tension and velocity of shortening of a muscle fiber increaseswith increasing preload, and the increase in contractile response of theheart with increasing preload is known as the Frank-Starling principle.When a myocardial region contracts late relative to other regions, thecontraction of those other regions stretches the later contractingregion and increases its preloading, thus causing an increase in thecontractile force generated by the region. Conversely, a myocardialregion that contracts earlier relative to other regions experiencesdecreased preloading and generates less contractile force. Becausepressure within the ventricles rises rapidly from a diastolic to asystolic value as blood is pumped out into the aorta and pulmonaryarteries, the parts of the ventricles that contract earlier duringsystole do so against a lower afterload than do parts of the ventriclescontracting later. Thus, if a ventricular region can be made to contractearlier than parts of the ventricle, it will be subjected to both adecreased preload and afterload which decreases the mechanical stressexperienced by the region relative to other regions during systoliccontraction. The region will also do less work thus lessening itsmetabolic demands and the degree of any ischemia that may be present.

In order to cause early contraction and lessened stress,electrostimulatory pacing pulses may be delivered to one or more sitesin or around the infarct in a manner that pre-excites those sitesrelative to the rest of the ventricle. (As the term is used herein, apacing pulse is any electrical stimulation of the heart of sufficientenergy to initiate a propagating depolarization, whether or not intendedto enforce a particular heart rate.) In a normal heartbeat, thespecialized His-Purkinje conduction network of the heart rapidlyconducts excitatory impulses from the sino-atrial node to theatrio-ventricular node, and thence to the ventricular myocardium toresult in a coordinated contraction of both ventricles. Artificialpacing with an electrode fixed into an area of the myocardium does nottake advantage of the heart's normal specialized conduction system forconducting excitation throughout the ventricles because the specializedconduction system can only be entered by impulses emanating from theatrio-ventricular node. Thus the spread of excitation from a ventricularpacing site must proceed only via the much slower conducting ventricularmuscle fibers, resulting in the part of the ventricular myocardiumstimulated by the pacing electrode contracting well before parts of theventricle located more distally to the electrode. This pre-excitation ofa paced site relative to other sites can be used to deliberately changethe distribution of wall stress experienced by the ventricle during thecardiac pumping cycle. Pre-excitation of the infarct region relative toother regions unloads the infarct region from mechanical stress bydecreasing its afterload and preload, thus preventing or minimizing theremodeling that would otherwise occur. In addition, because thecontractility of the infarct region is impaired, pre-excitation of theregion results in a resynchronized ventricular contraction that ishemodynamically more effective. Decreasing the wall stress of theinfarct region also lessens its oxygen requirements and lessens theprobability of an arrhythmia arising in the region.

Pacing therapy to unload the infarct region may be implemented by pacingthe ventricles at a single site in proximity to the infarct region or bypacing at multiple ventricular sites in such proximity. In the lattercase, the pacing pulses may be delivered to the multiple sitessimultaneously or in a defined pulse output sequence. As describedbelow, the single-site or multiple site pacing may be performed inaccordance with a bradycardia pacing algorithm such as an inhibiteddemand mode or a triggered mode.

1. Exemplary Implantable Device Description

A block diagram of an exemplary pacemaker for delivering pre-excitationpacing therapy to a site or sites in proximity to an infarct asdescribed above is illustrated in FIG. 1. Pacemakers are usuallyimplanted subcutaneously in the patient's chest and connected tosensing/pacing electrodes by leads either threaded through the vesselsof the upper venous system to the heart or by leads that penetrate thechest wall. (As the term is used herein, a “pacemaker” should be takento mean any cardiac rhythm management device with a pacing functionalityregardless of any other functions it may perform.) The controller of thepacemaker is made up of a microprocessor 10 communicating with a memory12 via a bidirectional data bus, where the memory 12 typically comprisesa ROM (read-only memory) for program storage and a RAM (random-accessmemory) for data storage. The controller could be implemented by othertypes of logic circuitry (e.g., discrete components or programmablelogic arrays) using a state machine type of design, but amicroprocessor-based system is preferable. The controller is capable ofoperating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and expiration of time intervals. A telemetry unit 80 isalso provided for communicating with an external programmer or, asdescribed below, with a system for applying counterpulsation therapy.

The device illustrated in FIG. 1 has multiple sensing and pacingchannels and is therefore capable of delivering single-site or multiplesite ventricular pacing. The multiple sensing and pacing channels may beconfigured as either atrial or ventricular channels allowing the deviceto deliver such pacing with or without atrial tracking. Shown in FIG. 5is a configuration with one atrial sensing/pacing channel and threeventricular sensing/pacing channels. The atrial sensing/pacing channelcomprises ring electrode 53 a, tip electrode 53 b, sense amplifier 51,pulse generator 52, and an atrial channel interface 50 whichcommunicates bidirectionally with a port of microprocessor 10. The threeventricular sensing/pacing channels that include ring electrodes 23 a,33 a, and 43 a, tip electrodes 23 b, 33 b, and 43 b, sense amplifiers21, 31, and 41, pulse generators 22, 32, and 42, and ventricular channelinterfaces 20, 30, and 40. A pacing channel is made up of the pulsegenerator connected to the electrode while a sensing channel is made upof the sense amplifier connected to the electrode. The channelinterfaces include analog-to-digital converters for digitizing sensingsignal inputs from the sensing amplifiers, registers that can be writtento for adjusting the gain and threshold values of the sensingamplifiers, and registers for controlling the output of pacing pulsesand/or changing the pacing pulse amplitude. In certain patients, pacingof sites in proximity to an infarct or within ischemic regions may beless excitable than normal and require an increased pacing energy inorder to achieve capture (i.e., initiating of a propagating actionpotential). For each channel, the same electrode pair can be used forboth sensing and pacing. In this embodiment, bipolar leads that includetwo electrodes are used for outputting a pacing pulse and/or sensingintrinsic activity. Other embodiments may employ a single electrode forsensing and pacing in each channel, known as a unipolar lead. A MOSswitching network 70 controlled by the microprocessor is used to switchthe electrodes from the input of a sense amplifier to the output of apulse generator as well as configure sensing or pacing channels with theavailable electrodes.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controller10 interprets electrogram signals from the sensing channels and controlsthe delivery of paces in accordance with a pacing mode. The sensingcircuitry of the pacemaker generates atrial and ventricular electrogramsignals from the voltages sensed by the electrodes of a particularchannel. When an electrogram signal in an atrial or sensing channelexceeds a specified threshold, the controller detects an atrial orventricular sense, respectively, which pacing algorithms may employ totrigger or inhibit pacing.

Pre-excitation pacing of one or more ventricular sites in proximity toan infarct may be delivered with a bradycardia pacing mode, which refersto a pacing algorithm that enforces a certain minimum heart rate.Pacemakers can enforce a minimum heart rate either asynchronously orsynchronously. In asynchronous pacing, the heart is paced at a fixedrate irrespective of intrinsic cardiac activity. Because of the risk ofinducing an arrhythmia with asynchronous pacing, most pacemakers fortreating bradycardia are programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demandventricular pacing mode, the ventricle is paced during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. For example, a ventricularescape interval can be defined between ventricular events so as to berestarted with each ventricular sense or pace. The inverse of thisescape interval is the minimum rate at which the pacemaker will allowthe ventricles to beat, sometimes referred to as the lower rate limit(LRL). In an atrial tracking pacing mode, another ventricular escapeinterval is defined between atrial and ventricular events, referred toas the atrio-ventricular interval (AVI). The atrio-ventricular intervalis triggered by an atrial sense and stopped by a ventricular sense orpace. A ventricular pace is delivered upon expiration of theatrio-ventricular interval if no ventricular sense occurs before theexpiration. Because it is only paced beats that pre-excite the infarctregion, it may be desirable in certain patients to decrease the AVI tobe below the intrinsic PR interval (i.e., the normal time for anintrinsic ventricular beat to occur after an atrial sense) or increasethe LRL to be slightly above the patient's normal resting heart rate.

In the case where the pre-excitation pacing of the ventricle isdelivered at multiple sites, the sites may be paced simultaneously or inaccordance with a particular pulse output sequence that specifies theorder in which the sites are to be paced during a single beat. Asaforesaid, one of the benefits of pre-excitation pacing of the infarctregion is resynchronization of the contraction that results inhemodynamic improvement. In some patients, such resynchronization may bemore successful if multiple ventricular sites are paced in a specifiedsequence such that certain of the pacing sites are pre-excited earlierthan others during a single beat.

It was noted above that another benefit of pre-exciting ventriculartissue during systole is a reduction in its oxygen requirements, thuspreventing or alleviating ischemia in the infarct region. Pre-excitationpacing as described above may also be employed to unload ischemicregions in either the atria or ventricles that are not associated withan infarct, which may act to prevent the development of angina in thepatient or a subsequent infarct. Ischemic regions, whether or notassociated with an infarct, can be identified with an angiogram,thallium scan or an MRI perfusion scan, and sites within ischemicregions so identified can be selected as pacing sites.

In a further refinement, pre-excitation pacing therapy may be started,stopped, or modified based upon sensor measurements via sensor interface100. Such sensors can be incorporated into the sensing/pacing leads orotherwise disposed and may include, for example, sensors for measuringblood pressure, blood flow, electrical impedance, minute ventilation, oracoustic energy. For example, the pacemaker could measure the impedancebetween pairs of electrodes to detect wall motion or changes in wallthickness during the cardiac cycle. Separate pairs of electrodes can beused to produce impedance signals from both a paced region and anon-ischemic region, such as the right ventricle if the paced andischemic region is in the left ventricle. Ischemia in the paced regioncan then be monitored by comparing the timing of the contraction in thepaced region with the timing of the non-ischemic region. If thecontractions in the paced region is delayed or significantly prolonged,an increase in ischemia can be surmised, and pre-excitation pacing tothe area can either be started or increased. Conversely, if a decreasein ischemia is detected, pre-excitation pacing may either be stopped orreduced. Modifications to the pacing therapy can also be made inaccordance with detected changes in the wall thickness of the pacedregion. In another embodiment, an accelerometer or microphone on thepacing lead or in the device package may be used to sense the acousticenergy generated by the heart during a cardiac cycle. Changes in theamplitude or morphology of the acoustic energy signal may then be usedto infer changes in the wall motion and the efficiency of contractionand relaxation. The applied pre-excitation pacing therapy can then bemodified based upon this information. (See U.S. Pat. No. 6,058,329,hereby incorporated by reference.)

A device for delivering pre-excitation pacing therapy as described abovemay also have other functionality that can be of benefit to patientswith ischemic heart disease, such as cardioversion/defibrillation. Drugdelivery capability incorporated into the device may also be useful.FIG. 1 shows a drug delivery system 120 interfaced to the microprocessorwhich may take various forms. For example, to improve the efficacy ofthe pre-excitation therapy in preventing or minimizing remodeling, itmay be desirable to simultaneously treat the patient with ACE(angiotensin converting enzyme) inhibitors or beta-blockers. It may alsobe useful to deliver biological agents such as growth factors oranti-apoptotic factors directly to the infarct region. Such delivery maybe implemented by infusing the agent through a lumen in a pacing leadthat is disposed near the infarct.

2. Electrode Placement

In order to place one or more pacing electrodes in proximity to aninfarcted region, the area of the infarct can be identified by a numberof means, including ultrasonic imaging, PET scans, thallium scans, andMRI perfusion scans. In the case of a left ventricular infarct,epicardial leads can either be placed directly on the epicardium with athoracotomy (an open chest surgical operation) or a thorascopicprocedure, or leads can be threaded from the upper venous system into acardiac vein via the coronary sinus. (See, e.g., U.S. Pat. No. 5,935,160issued to Auricchio et al., and assigned to Cardiac Pacemakers, Inc.,which is hereby incorporated by reference.) FIG. 2 is an exemplarydepiction of two such leads L1 and L2 that are passed from a pacemakerPM through cardiac veins in the epicardium of the left ventricle so thatthe pacing electrodes E1 and E2 are disposed adjacent to the infarctregion INF. In the case of lead placement by a thoracotomy orthorascopic procedure, it is possible to dispose the electrodes in amanner that more precisely circumscribes or overlies the infarct region.FIG. 3 shows an example of multiple electrodes E1 through E4 placedaround the infarct region INF, where the electrodes may either beconnected to the pacemaker by a single lead or separate leads for eachelectrode. FIG. 4A shows another example of an electrode arrangementwhere the multiple electrodes E1 through E7 are incorporated into apatch P1 so as to surround or overlay the infarct region INF. FIG. 4Bshows another example of a patch P2 in which the electrode is a singlecontinuous conductor C1 that is designed to surround the infarct region.FIG. 4C shows an exemplary construction of the conductor C1 where areason the outer surface of the conductor are intermittently coated with aninsulating material IM so as to increase the current density at theuncoated regions when the conductor is energized. Such a higher currentdensity may be necessary in some cases to excite a myocardial regionwhich has been rendered less excitable by ischemia.

3. Counterpulsation Therapy

Another means by which myocardial wall stress may be reduced is throughthe application of counterpulsation therapy, applied either as externalcounterpulsation (ECP) or by intra-aortic balloon pumping (IABP). InIABP, a balloon is mounted on a vascular catheter, inserted into thefemoral artery, and positioned in the descending aorta just distal tothe left subclavian artery. The balloon catheter is then connected to adrive console having a pressurized gas reservoir (usually either heliumor carbon dioxide) and control mechanisms for alternately inflating anddeflating the balloon in synchronization with the patients' cardiaccycle. Inflation at the onset of diastole results in proximal and distaldisplacement of blood volume in the aorta. Then, during the isovolumiccontraction phase of systole (i.e., the brief time that the aortic valveis closed and the left ventricle continues to contract), the gas israpidly withdrawn to deflate the balloon. This reduces the pressure atthe aortic root when the aortic valve opens, thus decreasing theafterload which the heart sees during ventricular systole. In contrast,during diastole when the balloon is inflated, the diastolic pressurerises and pushes the blood in the aorta distally towards the lower partof the body (on one side of the balloon) and proximally toward the heartand into the coronary arteries (on the other side of the balloon). IABPthus decreases afterload and myocardial oxygen requirements while alsoaugmenting cardiac output and coronary perfusion pressure. The principleby which ECP works is similar except that the counterpulsation isapplied by compression of blood vessels rather than displacement ofblood. In ECP, inflatable cuffs are placed around a patient's lowerextremities and alternately inflated and deflated in synchronizationwith the cardiac cycle. ECP, like IABP, decreases afterload duringsystole. As discussed above, a decreased afterload during systoleresults in decreased myocardial wall stress and less stimulus forremodeling. When IABP or ECP is applied in conjunction withpre-excitation pacing therapy as described above, the resulting reducedstress environment creates a more favorable environment for thepreservation (anti-apoptotic) and regeneration of functional tissue, asapposed to non-functional scare tissue formation.

For counterpulsation to achieve optimal effects, inflation and deflationneed to be correctly timed to the patient's cardiac cycle. This may beaccomplished by either using the patient's ECG signal or the patient'sarterial waveform. In the former method, for example, deflation of theballoon may be triggered by the R wave of the patient's ECG signal. Whencounterpulsation is used in conjunction with pacing therapy, however,more precise control may be obtained by having the implantable pacemakercontrol the timing of inflation and deflation cycles. When the escapeintervals of the pacemaker are set such that nearly all heart beats arepaced ones, the pacemaker determines when the beats occur and can thenschedule inflation and deflation in an optimal manner. A system fordelivering therapy to reduce myocardial wall stress during systole couldtherefore include 1) an implantable cardiac rhythm management devicehaving one or more sensing channels for sensing intrinsic cardiacactivity, one or more pacing channels for delivering pacing pulses, acontroller for controlling the delivery of pacing pulses in accordancewith a pacing mode; 2 a counterpulsation device for reducing afterloadduring ventricular systole; and, 3) a telemetry link enablingcommunications between the counterpulsation device and the implantabledevice, wherein the controller of the implantable device is programmedto transmit signals via the telemetry link for controlling the operationof the counterpulsation device.

FIG. 5 shows an example of a system for delivering pre-excitation pacingtherapy in conjunction with IABP. In this system, an implantable cardiacdevice is configured to deliver pacing therapy and communicate with anIABP (or ECP) drive console via a telemetry link. An implantable pacingdevice 500 is shown with a pair of sensing/pacing leads 501 and 502which are inserted intravenously into the right atrium and leftventricle, respectively, for delivering pacing therapy. An IABP driveconsole 550 is shown as having a gas reservoir and flow controllers 551connected to a catheter 552 with a balloon 553 at its end which isinserted into the aorta. (In an alternate embodiment, an ECP driveconsole is used instead of the IABP drive console.) The drive console550 may also incorporate one or more patient sensors 560 for collectingphysiological data such as blood pressure and/or blood flow at selectedlocations and/or cardiac electrical activity (e.g., a surface ECG). Theflow controllers 551 are controlled by a microprocessor-based controller555 which also receives information from the patient sensors 560. TheIABP drive console also has a telemetry unit 554 which enablescommunication between the controller 555 and the implantable device 500.The telemetry link may be an inductively coupled link or a far-field RFlink. The implantable device is then programmed to send inflation anddeflation signals to the LABP controller 555 in synchronization with thepacing pulses it delivers. The implantable device 500 may also receiveinformation from the drive console 550 such as data collected or derivedfrom the patient sensors 560, which information may be used to adjustthe pre-excitation and/or counterpulsation therapy. Thus,counterpulsation therapy and/or pre-excitation therapy may be started,stopped, or otherwise modified in accordance with data received eitherfrom the implantable device sensor interface 100 or the patient sensors560 of the IABP drive console. In certain embodiments, the drive consolecontroller 555 may function as an external programmer or be interfacedto an external programmer to enable reprogramming of the implantabledevice during IABP therapy. Although it is contemplated that the systemwould be most useful in delivering combined pre-excitation pacingtherapy and LABP (or ECP) in order to maximally reduce myocardial wallstress (for the purpose of reducing remodeling and/or alleviatingcardiac ischemia), the pacing device 500 may instead deliver any type ofconventional pacing therapy while precisely controlling balloondeflation and inflation via the telemetry link.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

What is claimed is:
 1. A method for minimizing ventricular remodeling ina patient, comprising: delivering pacing pulses to one or more sites inproximity to an infarcted or ischemic area in a ventricle uponexpiration of an escape interval, wherein the pacing pulses aredelivered in a manner that pre-excites the site or sites in proximity tothe infarcted ischemia area relative to other areas of the ventricle;delivering counterpulsation therapy to reduce afterload duringventricular systole; and, synchronizing the counterpulsation therapywith the delivery of pacing pulses to the pre-excited site or sites bytiming cycles of the counterpulsation therapy to occur with respect toexpiration of the escape interval.
 2. The method of claim 1 wherein thecounterpulsation therapy is intra-aortic balloon pumping.
 3. The methodof claim 1 wherein the counterpulsation therapy is externalcounterpulsation.
 4. The method of claim 1 wherein paces are deliveredto multiple sites in proximity to the infarcted or ischemic area in anorder defined by a specified pulse output sequence.
 5. The method ofclaim 1 wherein the pacing pulses are delivered by an implantable devicewhich controls the timing of the counterpulsation therapy via atelemetry link.
 6. The method of claim 5 wherein the telemetry link is afar-field RF link.
 7. The method of claim 1 further comprisingcollecting physiological data via a patient sensor and modifying thedelivery of pre-excitation and/or counterpulsation therapy in accordancetherewith.
 8. The method of claim 7 wherein the patient sensor is ablood pressure sensor.
 9. The method of claim 1 further comprisingdetecting changes in wall motion and wall thickness in an area inproximity to the infarct and modifying the delivery of pre-excitationpacing and/or counterpulsation therapy in accordance therewith.
 10. Themethod of claim 1 further comprising sensing acoustic energy generatedby the heart during a cardiac cycle and modifying the delivery ofpre-excitation pacing and/or counterpulsation therapy in accordancetherewith.
 11. A system for delivering therapy to a patient in order toreduce myocardial wall stress during systole, comprising: an implantablecardiac rhythm management device having one or more sensing amplifiersfor incorporation into sensing channels for sensing intrinsic cardiacactivity, one or more pulse generators for incorporation into pacingchannels for delivering pacing pulses, a controller for controlling thedelivery of pacing pulses in accordance with a pacing mode; wherein thecontroller is programmed to deliver pacing pulses upon expiration of anescape interval; a counterpulsation device for reducing afterload duringventricular systole; a telemetry link enabling communications betweenthe counterpulsation device and the implantable device; and, wherein thecontroller of the implantable device is programmed to transmit signalsvia the telemetry link for controlling the operation of thecounterpulsation device and synchronize the counterpulsation therapywith the delivery of pacing pulses by timing cycles of counterpulsationto occur with respect to expiration of the escape interval.
 12. Thesystem of claim 11 wherein the counterpulsation device is anintra-aortic balloon pump.
 13. The system of claim 11 wherein thecounterpulsation device is an external counterpulsation device.
 14. Thesystem of claim 11 wherein the telemetry link is an inductively coupledlink.
 15. The system of claim 11 wherein the telemetry link is afar-field RF link.
 16. The system of claim 11 wherein thecounterpulsation device further comprises one or more patient sensorsfor collecting physiological data which is transmitted to theimplantable device via the telemetry link and used to modify thedelivery of pre-excitation and/or counterpulsation therapy.
 17. Thesystem of claim 16 wherein the patient sensor is a blood pressuresensor.
 18. The system of claim 11 wherein the implantable devicefurther comprises an impedance sensor for detecting changes in wallmotion and wall thickness in an area in proximity to the infarct andwherein the controller is programmed to modify the delivery ofpre-excitation pacing and/or counterpulsation therapy in accordancetherewith.
 19. The system of claim 11 wherein the implantable devicefurther comprises an acoustic sensor for sensing acoustic energygenerated by the heart during a cardiac cycle and wherein the controlleris programmed to modify the delivery of pre-excitation pacing and/orcounterpulsation therapy in accordance therewith.
 20. The system ofclaim 11 wherein the controller is configured to deliver paces tomultiple sites in an order defined by a specified pulse output sequence.